PROJECT SUMMARY Aerobic exercise (AE) has well documented health benefits to prevent cardiovascular diseases (CVD) such as heart diseases or stroke. However, there is very little evidence whether resistance exercise (RE) prevents CVD or modifies the development of CVD risk factors, independent of and combined with AE. In fact, the Federal Physical Activity Guidelines primarily focus on AE for health. There remains an important unanswered question: ?What type or combination of exercise is most effective for CVD prevention?? To answer this question, the goal of this study, ?Comparison of the Cardiovascular Benefits of Resistance, Aerobic, and Combined Exercise (Cardio-RACE)? is to test the hypothesis that RE and AE have independent CVD benefits, thus the combined RE plus AE have greater additive benefits than either RE or AE alone. To achieve this goal, the project includes two specific aims: AIM 1: To explore the comparative effectiveness of RE, AE, and combined exercise on incident CVD risk factors (hypertension, type 2 diabetes, hypercholesterolemia, and obesity) and CVD morbidity and mortality, by analyzing a large cohort data. AIM 2: To evaluate the independent and additive (combined) effects of RE and AE training on traditional and emerging CVD risk factors/markers (central hemodynamics, inflammatory biomarkers, glucose metabolism, blood lipids, adiposity, sarcopenic indices, and fitness), by conducting a randomized controlled trial of exercise. In Aim 1, the Aerobics Center Longitudinal Study data in >34,000 adults will be used. This is the largest cohort followed over 35 years with RE and objectively measured muscular strength. In Aim 2, 400 adults at high risk of developing CVD will be recruited and randomized to one of four 1-year intervention groups: 1) RE training only, 2) AE training only, 3) a combined RE plus AE training, or 4) no training control. The proposed project will investigate mechanisms of how RE and AE training modify traditional and emerging CVD risk factors/markers (Aim 2), and further prevent CVD morbidity and mortality in the general population (Aim 1). This study could fill an important gap in our knowledge of the benefits of RE to further prevent CVD, beyond the well-documented benefits of AE. This project potentially contributes to developing more effective clinical and public health strategies to prevent CVD and advancing more comprehensive future physical activity guidelines to support the mission of the National Institutes of Health.